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1.
Magnes Res ; 31(1): 11-23, 2018 Feb 01.
Article in English | MEDLINE | ID: mdl-29991461

ABSTRACT

Tubulo-interstitial nephropathy (TIN) is a critical pathological setting for the renal prognosis, and an increase in the urine magnesium excretion is a well-known characteristic feature as one of clinical parametets for the assessment of TIN. We examined the correlation between the development of TIN and the changes in the mRNA expression of renal magnesium-transporting molecules in rats with unilateral ureter obstruction (UUO). Ureter-ligated kidney was sampled at day-0 (control), day-1 (early phase) and day-7 (late phase). The development of TIN was assessed by immunohistochemistry and the real-time PCR of fibrosis-related genes (MCP-1: 105.1 ± 14.8% on day-0, 132.9 ± 25.7% on day-1, 302.7 ± 32.7% on day-7, TGF-ß: 101.1 ± 7.6% on day-0, 93.6 ± 4.1% on day-1, 338.9 ± 20.7% on day-7) . The respective expressions of claudin-10, 14, 16, 19, and transient receptor potential (TRP) M6 as magnesium-transporting molecules were also studied. The expression of calcium sensing receptor (CaSR) as an inhibitory regulator of claudin-14 was additionally studied. The gene expression of claudin-16 was decreased in the late phase of UUO (100.2 ± 2.9% at day-0, 90.3 ± 6.3% at day-1, 36.4 ± 1.6% at day-7) which was consistent with the increased urine magnesium excretion. Immunohistochemistry showed an apparent reduction of the immunoreactivity of claudin-16 in the late phase. The expression of TRPM6 was reduced even in the early phase. The immunohistochemistry and gene expression of MCP-1 and TGF-ß showed that TIN was not apparent in the early phase but was significant in the late phase of UUO. The density of peritubular capillaries was diminished in the late phase but not in the early phase. Expression of claudin-14 and CaSR was up- and down-regulated, respectively. Our findings may indicate that the characteristic hypermagnesiuria in TIN is principally caused by the dysfunction of magnesium reabsorption in the thick ascending limb of Henle resulting from a significant decrease in the claudin-16 expression. The down-regulation might be closely related to the development of TIN.


Subject(s)
Claudins/genetics , Down-Regulation , Kidney Diseases/genetics , Kidney Diseases/urine , Kidney Tubules/pathology , Magnesium/urine , Animals , Biological Transport/genetics , Capillaries/metabolism , Capillaries/pathology , Claudins/metabolism , Disease Models, Animal , Down-Regulation/genetics , Kidney Diseases/pathology , Male , Rats, Sprague-Dawley , Receptors, Calcium-Sensing/genetics , Receptors, Calcium-Sensing/metabolism , Sodium Chloride/metabolism , Solute Carrier Family 12, Member 3/genetics , Solute Carrier Family 12, Member 3/metabolism , TRPM Cation Channels/genetics , TRPM Cation Channels/metabolism , Ureteral Obstruction/genetics , Ureteral Obstruction/urine , Water/metabolism
2.
Clin Exp Nephrol ; 19(6): 1071-8, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25724126

ABSTRACT

BACKGROUND: Elevated urine Mg excretion and its correlation with histological damage in tubulo-interstitial nephropathy (TIN) were reported. Here we investigated the clinical significance of the fractional excretion of Mg (FEMg) for the prediction of TIN. METHODS: We enrolled and assessed 94 adult patients with various renal diseases diagnosed principally by renal biopsy. RESULTS: Our stratified analysis based on the value of the conventional TIN parameter N-acetylglucosaminidase (NAG) excretion showed that the high-NAG index group (more than median value of NAG-to-Cr ratio, n = 47) demonstrated significantly high FEMg values (p = 0.017). A univariate analysis revealed a significant correlation between the FEMg and the NAG index (R = 0.60) but not for other parameters. A multivariate regression analysis confirmed the significance of the FEMg as an effective predictor of the NAG index. The FEMg showed a significant correlation with the estimated glomerular filtration rate (eGFR) in the patients with eGFR ≤ 30 mL/min. The correlation of FEMg with the NAG index was not observed in the primary glomerulonephritis patients but was apparent in the patients with hypertensive nephrosclerosis or interstitial nephritis. CONCLUSION: Our findings may indicate that the combination of the FEMg and the NAG index can provide a specific, sensitive assessment for TIN in patients without renal insufficiency.


Subject(s)
Magnesium/urine , Nephritis, Interstitial/urine , Acetylglucosaminidase/urine , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Nephritis, Interstitial/pathology , Predictive Value of Tests , Young Adult , beta 2-Microglobulin/urine
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